Retinal vascular diseases remain a common cause of vision loss and blindness with diabetes as the most common condition leading to retinopathy in adults in Western society. In particular, with type 1 diabetes the majority of patients will develo diabetic retinopathy (DR) with about 20-30% becoming legally blind while in type 2 diabetes more than 60% of patients will exhibit DR. With the well-documented global epidemic of type 2 diabetes, DR is likely to increase in incidence and prevalence since over 360 million people world-wide are projected to suffer from diabetes by 2030. Although therapies such as anti-VEGF agents and laser are currently available to treat macular edema and neovascularization, there is no treatment that regenerates damaged retinal vasculature with reestablishment of critical levels of blood flow needed to support & sustain recovery. Research over the last decade has shown that peripheral blood (PB)-derived CD34+ stem/progenitor cells are capable of homing to vascular lesions in the eye and contribute to vascular repair. Unfortunately, though in diabetic patients these CD34+ cells are defective as reflected by a profound inability to migrate in vitro due to an adhesion deficit. To overcome this deficit we explored the effect of treatment with a new technology, ASC-101, from America Stem Cell (ASC). Our preliminary in vivo studies with mice show that ASC-101-mediated fucosylation of PB-derived CD34+ cells obtained from diabetic patients led to enhanced homing of these cells to damaged retinal vessels post ischemia/reperfusion (I/R) by comparison to controls. Our present SBIR submission will extend on these initial exciting proof-of-concept results with the identification of optimal parameters fo application along with defining the enduring nature and functional significance of this apparent restorative effect. Thus, we have outlined three specific aims: 1.Manufacture research-grade ASC-101 and substrate, GDP-fucose 2.Optimize treatment parameters, profile enduring effect & confirm role of homing to enhanced effect. 3.Examine for functional improvement Positive results from our presently proposed experiments will support subsequent submission of an SBIR II to conduct additional studies further addressing application of this novel stem-cell-based approach in addition to addressing IND-enabling activities in preparation for an eventual clinical trial involving patients with retinal disease.